FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
International journal of molecular sciences2024; 25(10); 5210; doi: 10.3390/ijms25105210

Immunology of Physical Exercise: Is Equus caballus an Appropriate Animal Model for Human Athletes?

Abstract: Domestic horses routinely participate in vigorous and various athletic activities. This enables the horse to serve as a model for studying athletic physiology and immunology in other species, including humans. For instance, as a model of physical efforts, such as endurance rides (long-distance running/aerobic exercise) and races (anaerobic exercise), the horse can be useful in evaluating post-exercise response. Currently, there has been significant interest in finding biomarkers, which characterize the advancement of training and adaptation to physical exercise in the horse. The parallels in cellular responses to physical exercises, such as changes in receptor expression and blood cell activity, improve our understanding of the mechanisms involved in the body's response to intense physical activity. This study focuses on the changes in levels of the pro- and anti-inflammatory cytokines and cellular response in the context of post-exercise immune response. Both the direction of changes in cytokine levels and cellular responses of the body, such as proliferation and expression of surface markers on lymphocytes, monocytes and neutrophils, show cross-functional similarities. This review reveals that horses are robust research models for studying the immune response to physical exercise in human athletes.
Get Full Text
Publication Date: 2024-05-10 PubMed ID: 38791248PubMed Central: PMC11121269DOI: 10.3390/ijms25105210Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Review

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The article discusses the use of horses, specifically Equus caballus, as valuable models for studying the immune response to physical exercise in humans due to the similarities in the body’s cellular and hormonal responses to intense training.

Emphasis on Horse as an Animal Model

  • The article initially emphasizes the suitability of the domestic horse as a model organism for athletics. The authors highlight the relevance of this model due to the variety and intensity of athletic activities horses commonly participate in, similar to human sports.
  • The question of whether a horse is an appropriate model for human athletes is introduced with a focus on studying cellular responses and biochemical changes related to different forms of physical exercise.

Understanding Physical Efforts

  • The paper uses horses for modeling various forms of physical exercise, focusing specifically on long-distance running (aerobic exercise) and races (anaerobic exercise).
  • The authors discuss these variations of physical exercises and their distinct impact on the post-exercise response, which can provide an understanding of how the human body might react under similar stressful situations.

Exploration of Biomarkers

  • There is a notable mention of the interest in identifying biomarkers that could monitor training progress and adaptation in horses. Finding such markers could be helpful for human athletes as well, providing a measurable indication of the physiological changes occurring due to training and exercise.

Pro- and Anti-inflammatory Cytokines

  • The core of the study revolves around changes in pro- and anti-inflammatory cytokines, which are small proteins released by cells that have a specific effect on the interactions and communications between cells.
  • The authors emphasize the correlation between the levels of these cytokines and the cellular immune response after exercise.

Cellular Responses during Exercise

  • In addition to hormonal changes, the paper highlights the change in expression of surface markers on lymphocytes, monocytes, and neutrophils (types of white blood cells), which are integral to the immune response.
  • These cellular responses offer another dimension of understanding the impact of strenuous physical activity on the body and immune system.

Final Findings

  • The conclusion from reviewing relevant literature is that horses are a robust and relevant model for studying the immune response to physical exercise in human athletes due to considerable similarities in cellular and hormonal responses.

Cite This Article

APA
Witkowska-Piłaszewicz O, Malin K, Dąbrowska I, Grzędzicka J, Ostaszewski P, Carter C. (2024). Immunology of Physical Exercise: Is Equus caballus an Appropriate Animal Model for Human Athletes? Int J Mol Sci, 25(10), 5210. https://doi.org/10.3390/ijms25105210

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 25
Issue: 10
PII: 5210

Researcher Affiliations

Witkowska-Piłaszewicz, Olga
  • Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland.
Malin, Katarzyna
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Dąbrowska, Izabela
  • Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland.
Grzędzicka, Jowita
  • Department of Large Animals Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland.
Ostaszewski, Piotr
  • Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, Poland.
Carter, Craig
  • Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, KY 40506, USA.

MeSH Terms

  • Animals
  • Horses / immunology
  • Humans
  • Physical Conditioning, Animal
  • Athletes
  • Cytokines / metabolism
  • Models, Animal
  • Exercise / physiology
  • Biomarkers

Grant Funding

  • 2021/41/B/NZ7/03548 / National Science Center

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 186 references
  1. Lee E.C., Fragala M.S., Kavouras S.A., Queen R.M., Pryor J.L., Casa D.J.. Biomarkers in Sports and Exercise: Tracking Health, Performance, and Recovery in Athletes. J. Strength Cond. Res. 2017;31:2920–2937.
    doi: 10.1519/JSC.0000000000002122pmc: PMC5640004pubmed: 28737585google scholar: lookup
  2. Ericsson A.C., Crim M.J., Franklin C.L.. A brief history of animal modeling. Mo. Med. 2013;110:201–205.
    pmc: PMC3979591pubmed: 23829102
  3. Sarrafian T.L., Garcia T.C., Dienes E.E., Murphy B., Stover S.M., Galuppo L.D.. A Nonterminal Equine Mandibular Model of Bone Healing. Vet. Surg. 2015;44:314–321.
    doi: 10.1111/j.1532-950x.2014.12279.xpubmed: 25258299google scholar: lookup
  4. Smith R.K., Garvican E.R., Fortier L.A.. The current ‘state of play’ of regenerative medicine in horses: What the horse can tell the human. Regen. Med. 2014;9:673–685.
    doi: 10.2217/rme.14.42pubmed: 25372081google scholar: lookup
  5. Brehm W., Burk J., Delling U.. Application of Stem Cells for the Treatment of Joint Disease in Horses. 2014. pp. 215–228. Methods in Molecular Biology.
    doi: 10.1007/978-1-4939-1453-1_18pubmed: 25173386google scholar: lookup
  6. McIlwraith C.W., Frisbie D.D., Kawcak C.E.. The horse as a model of naturally occurring osteoarthritis. Bone Jt. Res. 2012;1:297–309.
    doi: 10.1302/2046-3758.111.2000132pmc: PMC3626203pubmed: 23610661google scholar: lookup
  7. Patterson-Kane J.C., Becker D.L., Rich T.. The Pathogenesis of Tendon Microdamage in Athletes: The Horse as a Natural Model for Basic Cellular Research. J. Comp. Pathol. 2012;147:227–247.
    doi: 10.1016/j.jcpa.2012.05.010pubmed: 22789861google scholar: lookup
  8. Iwamoto J., Takeda T.. Stress fractures in athletes: Review of 196 cases. J. Orthop. Sci. 2003;8:273–278.
    doi: 10.1007/s10776-002-0632-5pubmed: 12768465google scholar: lookup
  9. Välimäki V.V., Alfthan H., Lehmuskallio E., Löyttyniemi E., Sahi T., Suominen H., Välimäki M.J.. Risk factors for clinical stress fractures in male military recruits: A prospective cohort study. Bone. 2005;37:267–273.
    doi: 10.1016/j.bone.2005.04.016pubmed: 15964254google scholar: lookup
  10. Witkowska-Piłaszewicz O., Bąska P., Czopowicz M., Żmigrodzka M., Szarska E., Szczepaniak J., Nowak Z., Winnicka A., Cywińska A.. Anti-Inflammatory State in Arabian Horses Introduced to the Endurance Training. Animals 2019;9:616.
    doi: 10.3390/ani9090616pmc: PMC6769738pubmed: 31462005google scholar: lookup
  11. Witkowska-Piłaszewicz O., Pingwara R., Winnicka A.. The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses. Antioxidants 2020;9:1155.
    doi: 10.3390/antiox9111155pmc: PMC7699811pubmed: 33233549google scholar: lookup
  12. Horohov D.W.. The equine immune responses to infectious and allergic disease: A model for humans?. Mol. Immunol. 2015;66:89–96.
    doi: 10.1016/j.molimm.2014.09.020pubmed: 25457878google scholar: lookup
  13. Hinchcliff K.W., Kaneps A.J., Geor R.J.. Equine Exercise Physiology: The Science of Exercise in the Athletic Horse. 2008. 463p.
  14. Scheffer D.d.L., Latini A.. Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs. Biochim. Et Biophys. Acta (BBA)—Mol. Basis Dis. 2020;1866:165823.
    doi: 10.1016/j.bbadis.2020.165823pmc: PMC7188661pubmed: 32360589google scholar: lookup
  15. Kakanis M., Peake J., Hooper S., Gray B., Marshall-Gradisnik S.. The open window of susceptibility to infection after acute exercise in healthy young male elite athletes. J. Sci. Med. Sport. 2010;13:e85–e86.
    doi: 10.1016/j.jsams.2010.10.642pubmed: 20839496google scholar: lookup
  16. Campbell J.P., Turner J.E.. Debunking the Myth of Exercise-Induced Immune Suppression: Redefining the Impact of Exercise on Immunological Health across the Lifespan. Front. Immunol. 2018;9:648.
    doi: 10.3389/fimmu.2018.00648pmc: PMC5911985pubmed: 29713319google scholar: lookup
  17. Gleeson M., Bishop N., Oliveira M., McCauley T., Tauler P., Muhamad A.S.. Respiratory infection risk in athletes: Association with antigen-stimulated IL-10 production and salivary IgA secretion. Scand. J. Med. Sci. Sports. 2012;22:410–417.
    doi: 10.1111/j.1600-0838.2010.01272.xpubmed: 21385218google scholar: lookup
  18. Shaw D.M., Merien F., Braakhuis A., Dulson D.. T-cells and their cytokine production: The anti-inflammatory and immunosuppressive effects of strenuous exercise. Cytokine 2018;104:136–142.
    doi: 10.1016/j.cyto.2017.10.001pubmed: 29021092google scholar: lookup
  19. Folsom R.W., Littlefield-Chabaud M.A., French D.D., Pourciau S.S., Mistric L., Horohov D.W.. Exercise alters the immune response to equine influenza virus and increases susceptibility to infection. Equine Vet. J. 2001;33:664–669.
    doi: 10.2746/042516401776249417pubmed: 11770987google scholar: lookup
  20. Carvallo F.R., Uzal F.A., Diab S.S., Hill A.E., Arthur R.M.. Retrospective study of fatal pneumonia in racehorses. J. Vet. Diagn. Investig. 2017;29:450–456.
    doi: 10.1177/1040638717717290pubmed: 28681687google scholar: lookup
  21. Raidal S., Love D., Bailey G.. Effect of a single bout of high intensity exercise on lower respiratory tract contamination in the horse. Aust. Vet. J. 1997;75:293–295.
    doi: 10.1111/j.1751-0813.1997.tb10101.xpubmed: 9140658google scholar: lookup
  22. Wood J.L.N., Newton J.R., Chanter N., Mumford J.A.. Association between Respiratory Disease and Bacterial and Viral Infections in British Racehorses. J. Clin. Microbiol. 2005;43:120–126.
    doi: 10.1128/jcm.43.1.120-126.2005pmc: PMC540098pubmed: 15634959google scholar: lookup
  23. Mårtensson S., Nordebo K., Malm C.. High Training Volumes are Associated with a Low Number of Self-Reported Sick Days in Elite Endurance Athletes. J. Sports Sci. Med. 2014;13:929–933.
    pmc: PMC4234964pubmed: 25435787
  24. Pedersen B.K., Saltin B.. Exercise as medicine—Evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand. J. Med. Sci. Sports. 2015;25:1–72.
    doi: 10.1111/sms.12581pubmed: 26606383google scholar: lookup
  25. Nieman D.C., Henson D.A., Austin M.D., Sha W.. Upper respiratory tract infection is reduced in physically fit and active adults. Br. J. Sports Med. 2011;45:987–992.
    doi: 10.1136/bjsm.2010.077875pubmed: 21041243google scholar: lookup
  26. Hoffman J.. Physiological Aspects of Sport Training and Performance. 2014. 505p.
  27. Gleeson L.E., Sheedy F.J.. Metabolic reprogramming & inflammation: Fuelling the host response to pathogens. Semin. Immunol. 2016;28:450–468.
    doi: 10.1016/j.smim.2016.10.007pubmed: 27780657google scholar: lookup
  28. da Silveira M.P., da Silva Fagundes K.K., Bizuti M.R., Starck É., Rossi R.C., de Resende e Silva D.T.. Physical exercise as a tool to help the immune system against COVID-19: An integrative review of the current literature. Clin. Exp. Med. 2021;21:15–28.
    doi: 10.1007/s10238-020-00650-3pmc: PMC7387807pubmed: 32728975google scholar: lookup
  29. Horohov D.W., Sinatra S.T., Chopra R.K., Jankowitz S., Betancourt A., Bloomer R.J.. The Effect of Exercise and Nutritional Supplementation on Proinflammatory Cytokine Expression in Young Racehorses during Training. J. Equine Vet. Sci. 2012;32:805–815.
    doi: 10.1016/j.jevs.2012.03.017google scholar: lookup
  30. McKeever K.H., Arent S.M., Davitt P.. The Athletic Horse. 2014. Endocrine and immune responses to exercise and training; pp. 88–107.
  31. Silveira L.S., Antunes B.d.M.M., Minari A.L.A., dos Santos R.V.T., Neto J.C.R., Lira F.S.. Macrophage Polarization: Implications on Metabolic Diseases and the Role of Exercise. Crit. Rev. Eukaryot. Gene Expr. 2016;26:115–132.
    doi: 10.1615/CritRevEukaryotGeneExpr.2016015920pubmed: 27480774google scholar: lookup
  32. Arfuso F., Giannetto C., Fazio F., Panzera F., Piccione G.. Training Program Intensity Induces an Acute Phase Response in Clinically Healthy Horses. J. Equine Vet. Sci. 2020;88:102986.
    doi: 10.1016/j.jevs.2020.102986pubmed: 32303313google scholar: lookup
  33. Kaspar F., Jelinek H.F., Perkins S., Al-Aubaidy H.A., DeJong B., Butkowski E.. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study. Mediat. Inflamm. 2016;2016:5474837.
    doi: 10.1155/2016/5474837pmc: PMC4861798pubmed: 27212809google scholar: lookup
  34. Allen J., Sun Y., Woods J.A.. Progress in Molecular Biology and Translational Science. 2015. Exercise and the Regulation of Inflammatory Responses; pp. 337–354.
    pubmed: 26477921
  35. Cerqueira É., Marinho D.A., Neiva H.P., Lourenço O.. Inflammatory Effects of High and Moderate Intensity Exercise—A Systematic Review. Front. Physiol. 2020;10:1550.
    doi: 10.3389/fphys.2019.01550pmc: PMC6962351pubmed: 31992987google scholar: lookup
  36. Witkowska-Piłaszewicz O., Bąska P., Czopowicz M., Żmigrodzka M., Szczepaniak J., Szarska E., Winnicka A., Cywińska A.. Changes in Serum Amyloid A (SAA) Concentration in Arabian Endurance Horses during First Training Season. Animals 2019;9:330.
    doi: 10.3390/ani9060330pmc: PMC6616404pubmed: 31181740google scholar: lookup
  37. Cywinska A., Witkowski L., Szarska E., Schollenberger A., Winnicka A.. Serum amyloid A (SAA) concentration after training sessions in Arabian race and endurance horses. BMC Vet. Res. 2013;9:91.
    doi: 10.1186/1746-6148-9-91pmc: PMC3655847pubmed: 23634727google scholar: lookup
  38. Siqueira R.F.d., Fernandes W.R.. Post-ride inflammatory markers in endurance horses. Cienc. Rural. 2016;46:1256–1261.
    doi: 10.1590/0103-8478cr20151070google scholar: lookup
  39. Cywińska A., Szarska E., Górecka R., Witkowski L., Hecold M., Bereznowski A., Schollenberger A., Winnicka A.. Acute phase protein concentrations after limited distance and long distance endurance rides in horses. Res. Vet. Sci. 2012;93:1402–1406.
    doi: 10.1016/j.rvsc.2012.02.008pubmed: 22390917google scholar: lookup
  40. Grzędzicka J., Dąbrowska I., Malin K., Witkowska-Piłaszewicz O.. Exercise-related changes in the anabolic index (testosterone to cortisol ratio) and serum amyloid A concentration in endurance and racehorses at different fitness levels. Front. Vet. Sci. 2023;10:1148990.
    doi: 10.3389/fvets.2023.1148990pmc: PMC10150884pubmed: 37138908google scholar: lookup
  41. Giori L., Moretti P., Giordano A., Paltrinieri S.. Short-term Evaluation of Serum Amyloid A after Exercise in Clinically Healthy Horses. J. Equine Vet. Sci. 2011;31:499–501.
    doi: 10.1016/j.jevs.2011.05.008google scholar: lookup
  42. Kristensen L., Buhl R., Nostell K., Bak L., Petersen E., Lindholm M., Jacobsen S.. Acute exercise does not induce an acute phase response (APR) in Standardbred trotters. Can. J. Vet. Res. 2014;78:97–102.
    pmc: PMC3962284pubmed: 24688170
  43. Turło A., Cywińska A., Czopowicz M., Witkowski L., Jaśkiewicz A., Winnicka A.. Racing Induces Changes in the Blood Concentration of Serum Amyloid A in Thoroughbred Racehorses. J. Equine Vet. Sci. 2016;36:15–18.
    doi: 10.1016/j.jevs.2015.09.008google scholar: lookup
  44. Fedewa M.V., Hathaway E.D., Ward-Ritacco C.L.. Effect of exercise training on C reactive protein: A systematic review and meta-analysis of randomised and non-randomised controlled trials. Br. J. Sports Med. 2017;51:670–676.
    doi: 10.1136/bjsports-2016-095999pubmed: 27445361google scholar: lookup
  45. Mihelić K., Vrbanac Z., Bojanić K., Kostanjšak T., Ljubić B.B., Gotić J., Vnuk D., Bottegaro N.B.. Changes in Acute Phase Response Biomarkers in Racing Endurance Horses. Animals 2022;12:2993.
    doi: 10.3390/ani12212993pmc: PMC9657625pubmed: 36359117google scholar: lookup
  46. di Masi A., De Simone G., Ciaccio C., D’Orso S., Coletta M., Ascenzi P.. Haptoglobin: From hemoglobin scavenging to human health. Mol. Asp. Med. 2020;73:100851.
    doi: 10.1016/j.mam.2020.100851pubmed: 32660714google scholar: lookup
  47. Lippi G., Sanchis-Gomar F.. Epidemiological, biological and clinical update on exercise-induced hemolysis. Ann. Transl. Med. 2019;7:270.
    doi: 10.21037/atm.2019.05.41pmc: PMC6614330pubmed: 31355237google scholar: lookup
  48. Davidson R., Robertson J., Galea G., Maughan R.. Hematological Changes Associated with Marathon Running. Int. J. Sports Med. 1987;8:19–25.
    doi: 10.1055/s-2008-1025634pubmed: 3557778google scholar: lookup
  49. Olaf Schumacher Y., Schmid A., Grathwohl D., Bültermann D., Berg A.. Hematological indices and iron status in athletes of various sports and performances. Med. Sci. Sports Exerc. 2002;34:869–875.
    doi: 10.1097/00005768-200205000-00022pubmed: 11984308google scholar: lookup
  50. Binnie M.J., Dawson B., Pinnington H., Landers G., Peeling P.. Part 2: Effect of Training Surface on Acute Physiological Responses after Sport-Specific Training. J. Strength Cond. Res. 2013;27:1057–1066.
    doi: 10.1519/JSC.0b013e3182651d63pubmed: 22843041google scholar: lookup
  51. Masini A.P., Tedeschi D., Baragli P., Sighieri C., Lubas G.. Exercise-induced intravascular haemolysis in standardbred horses. Comp. Clin. Pathol. 2003;12:45–48.
    doi: 10.1007/s00580-002-0470-ygoogle scholar: lookup
  52. Cywinska A., Szarska E., Kowalska A., Ostaszewski P., Schollenberger A.. Gender differences in exercise-induced intravascular haemolysis during race training in thoroughbred horses. Res. Vet. Sci. 2011;90:133–137.
    doi: 10.1016/j.rvsc.2010.05.004pubmed: 20553886google scholar: lookup
  53. Docherty S., Harley R., McAuley J.J., Crowe L.A.N., Pedret C., Kirwan P.D., Siebert S., Millar N.L.. The effect of exercise on cytokines: Implications for musculoskeletal health: A narrative review. BMC Sports Sci. Med. Rehabil. 2022;14:5.
    doi: 10.1186/s13102-022-00397-2pmc: PMC8740100pubmed: 34991697google scholar: lookup
  54. Liburt N.R., Adams A.A., Betancourt A., Horohov D.W., McKeever K.H.. Exercise-induced increases in inflammatory cytokines in muscle and blood of horses. Equine Vet. J. 2010;42:280–288.
    doi: 10.1111/j.2042-3306.2010.00275.xpubmed: 21059019google scholar: lookup
  55. Sohail M.U., Al-Mansoori L., Al-Jaber H., Georgakopoulos C., Donati F., Botrè F., Sellami M., Elrayess M.A.. Assessment of Serum Cytokines and Oxidative Stress Markers in Elite Athletes Reveals Unique Profiles Associated with Different Sport Disciplines. Front. Physiol. 2020;11:600888.
    doi: 10.3389/fphys.2020.600888pmc: PMC7593763pubmed: 33178053google scholar: lookup
  56. Lee H.G., Choi J.-Y., Park J.-W., Park T.S., Song K.-D., Shin D., Cho B.-W.. Effects of exercise on myokine gene expression in horse skeletal muscles. Asian-Australas. J. Anim. Sci. 2019;32:350–356.
    doi: 10.5713/ajas.18.0375pmc: PMC6409466pubmed: 30208686google scholar: lookup
  57. Pedersen B.K., Åkerström T.C.A., Nielsen A.R., Fischer C.P.. Role of myokines in exercise and metabolism. J. Appl. Physiol. 2007;103:1093–1098.
    doi: 10.1152/japplphysiol.00080.2007pubmed: 17347387google scholar: lookup
  58. Ostrowski K., Rohde T., Zacho M., Asp S., Pedersen B.K.. Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running. J. Physiol. 1998;508:949–953.
    doi: 10.1111/j.1469-7793.1998.949bp.xpmc: PMC2230908pubmed: 9518745google scholar: lookup
  59. Barbosa L.P., da Silva Aguiar S., Santos P.A., dos Santos Rosa T., Maciel L.A., de Deus L.A., Neves R.V.P., de Araújo Leite P.L., Gutierrez S.D., Sousa C.V.. Relationship between inflammatory biomarkers and testosterone levels in male master athletes and non-athletes. Exp. Gerontol. 2021;151:111407.
    doi: 10.1016/j.exger.2021.111407pubmed: 34022273google scholar: lookup
  60. Baum M., Klöpping-Menke K., Müller-Steinhardt M., Liesen H.. Increased concentrations of interleukin 1-β in whole blood cultures supernatants after 12 weeks of moderate endurance exercise. Eur. J. Appl. Physiol. 1999;79:500–503.
    doi: 10.1007/s004210050544pubmed: 10344459google scholar: lookup
  61. Plisak U., Szczepaniak J., Żmigrodzka M., Giercuszkiewicz-Hecold B., Witkowska-Piłaszewicz O.. Changes in novel anti-infalmmatory cytokine concetration in the bood of endurance and race horses at different levels of training. Comput. Struct. Biotechnol. J. 2023;21:418–424.
    doi: 10.1016/j.csbj.2022.12.016pmc: PMC9798135pubmed: 36618977google scholar: lookup
  62. Moldoveanu A.I., Shephard R.J., Shek P.N.. The Cytokine Response to Physical Activity and Training. Sports Med. 2001;31:115–144.
    doi: 10.2165/00007256-200131020-00004pmc: PMC7101891pubmed: 11227979google scholar: lookup
  63. Cywińska A., Turło A., Witkowski L., Szarska E., Winnicka A.. Changes in blood cytokine concentrations in horses after long-distance endurance rides. Med. Weter. 2014;70:568–571.
  64. Nielsen H.G., Øktedalen O., Opstad P.-K., Lyberg T.. Plasma Cytokine Profiles in Long-Term Strenuous Exercise. J. Sports Med. 2016;2016:7186137.
    doi: 10.1155/2016/7186137pmc: PMC4864530pubmed: 27239554google scholar: lookup
  65. Carey A.L., Febbraio M.A.. Interleukin-6 and insulin sensitivity: Friend or foe?. Diabetologia. 2004;47:1135–1142.
    doi: 10.1007/s00125-004-1447-ypubmed: 15241593google scholar: lookup
  66. Fischer C.P.. Interleukin-6 in acute exercise and training: What is the biological relevance?. Exerc. Immunol. Rev. 2006;12:6–33.
    pubmed: 17201070
  67. Pedersen B.K., Febbraio M.A.. Muscle as an endocrine organ: Focus on muscle-derived interleukin-6. Physiol. Rev. 2008;88:1379–1406.
    doi: 10.1152/physrev.90100.2007pubmed: 18923185google scholar: lookup
  68. Sugama K., Suzuki K., Yoshitani K., Shiraishi K., Kometani T.. IL-17, neutrophil activation and muscle damage following endurance exercise. Exerc. Immunol. Rev. 2012;18:116–127.
    pubmed: 22876724
  69. Peake J.M., Della Gatta P., Suzuki K., Nieman D.C.. Cytokine expression and secretion by skeletal muscle cells: Regulatory mechanisms and exercise effects. Exerc. Immunol. Rev. 2015;21:8–25.
    pubmed: 25826432
  70. Margeli A., Skenderi K., Tsironi M., Hantzi E., Matalas A.-L., Vrettou C., Kanavakis E., Chrousos G., Papassotiriou I.. Dramatic Elevations of Interleukin-6 and Acute-Phase Reactants in Athletes Participating in the Ultradistance Foot Race Spartathlon: Severe Systemic Inflammation and Lipid and Lipoprotein Changes in Protracted Exercise. J. Clin. Endocrinol. Metab. 2005;90:3914–3918.
    doi: 10.1210/jc.2004-2346pubmed: 15855262google scholar: lookup
  71. Brenner I.K.M., Natale V.M., Vasiliou P., Moldoveanu A.I., Shek P.N., Shephard R.J.. Impact of three different types of exercise on components of the inflammatory response. Eur. J. Appl. Physiol. 1999;80:452–460.
    doi: 10.1007/s004210050617pubmed: 10502079google scholar: lookup
  72. Natelson B.H., Zhou X., Ottenweller J.E., Bergen M.T., Sisto S.A., Drastal S., Tapp W.N., Gause W.L.. Effect of Acute Exhausting Exercise on Cytokine Gene Expression in Men. Int. J. Sports Med. 1996;17:299–302.
    doi: 10.1055/s-2007-972850pubmed: 8814513google scholar: lookup
  73. Garbers C., Heink S., Korn T., Rose-John S.. Interleukin-6: Designing specific therapeutics for a complex cytokine. Nat. Rev. Drug Discov. 2018;17:395–412.
    doi: 10.1038/nrd.2018.45pubmed: 29725131google scholar: lookup
  74. Bury T., Louis R., Radermecker M., Pirnay F.. Blood Mononudear Cells Mobilization and Cytokines Secretion during Prolonged Exercises. Int. J. Sports Med. 1996;17:156–160.
    doi: 10.1055/s-2007-972825pubmed: 8833720google scholar: lookup
  75. Sprenger H., Jacobs C., Nain M., Gressner A.M., Prinz H., Wesemann W., Gemsa D.. Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long-distance running. Clin. Immunol. Immunopathol. 1992;63:188–195.
    doi: 10.1016/0090-1229(92)90012-Dpubmed: 1611721google scholar: lookup
  76. Suzuki K., Yamada M., Kurakake S., Okamura N., Yamaya K., Liu Q., Kudoh S., Kowatari K., Nakaji S., Sugawara K.. Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans. Eur. J. Appl. Physiol. 2000;81:281–287.
    doi: 10.1007/s004210050044pubmed: 10664086google scholar: lookup
  77. Ullum H., Haahr P.M., Diamant M., Palmo J., Halkjaer-Kristensen J., McGinnis G.R., Ballmann C., Peters B., Nanayakkara G., Roberts M.. Bicycle exercise enhances plasma IL-6 but does not change IL-1 alpha, IL-1 beta, IL-6, or TNF-alpha pre-mRNA in BMNC. J. Appl. Physiol. 1994;77:93–97.
    doi: 10.1152/jappl.1994.77.1.93pubmed: 7961280google scholar: lookup
  78. Smith L.L.. Cytokine hypothesis of overtraining: A physiological adaptation to excessive stress?. Med. Sci. Sports Exerc. 2000;32:317.
    doi: 10.1097/00005768-200002000-00011pubmed: 10694113google scholar: lookup
  79. Starkie R.L., Rolland J., Angus D.J., Anderson M.J., Febbraio M.A.. Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-α levels after prolonged running. Am. J. Physiol. Physiol. 2001;280:C769–C774.
    doi: 10.1152/ajpcell.2001.280.4.c769pubmed: 11245592google scholar: lookup
  80. Page A.E., Stewart J.C., Fielding C.L., Horohov D.W.. The Effect of a 160-Kilometer Competitive Endurance Ride on Inflammatory Marker mRNA Expression in Horses. J. Equine Vet. Sci. 2019;79:45–49.
    doi: 10.1016/j.jevs.2019.05.017pubmed: 31405499google scholar: lookup
  81. Londhe P., Davie J.K.. Interferon-γ Resets Muscle Cell Fate by Stimulating the Sequential Recruitment of JARID2 and PRC2 to Promoters to Repress Myogenesis. Sci. Signal. 2013;6:ra107.
    doi: 10.1126/scisignal.2004633pmc: PMC4000160pubmed: 24327761google scholar: lookup
  82. LaVoy E.C., Bosch J.A., Lowder T.W., Simpson R.J.. Acute aerobic exercise in humans increases cytokine expression in CD27− but not CD27+ CD8+ T-cells. Brain Behav. Immun. 2013;27:54–62.
    doi: 10.1016/j.bbi.2012.09.006pubmed: 23017234google scholar: lookup
  83. Farrar M.A., Schreiber R.D.. The Molecular Cell Biology of Interferon-γ and its Receptor. Annu. Rev. Immunol. 1993;11:571–611.
    doi: 10.1146/annurev.iy.11.040193.003035pubmed: 8476573google scholar: lookup
  84. Svensson M., Lexell J., Deierborg T.. Effects of Physical Exercise on Neuroinflammation, Neuroplasticity, Neurodegeneration, and Behavior: What We Can Learn From Animal Models in Clinical Settings. Neurorehabilit. Neural Repair. 2015;29:577–589.
    doi: 10.1177/1545968314562108pubmed: 25527485google scholar: lookup
  85. Wadley A.J., Chen Y.-W., Lip G.Y., Fisher J.P., Aldred S.. Low volume–high intensity interval exercise elicits antioxidant and anti-inflammatory effects in humans. J. Sports Sci. 2016;34:1–9.
    doi: 10.1080/02640414.2015.1035666pubmed: 25915178google scholar: lookup
  86. Ostrowski K., Rohde T., Asp S., Schjerling P., Pedersen B.K.. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J. Physiol. 1999;515:287–291.
    doi: 10.1111/j.1469-7793.1999.287ad.xpmc: PMC2269132pubmed: 9925898google scholar: lookup
  87. Steensberg A., Fischer C.P., Keller C., Møller K., Pedersen B.K.. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am. J. Physiol. Endocrinol. Metab. 2003;285:E433–E437.
    doi: 10.1152/ajpendo.00074.2003pubmed: 12857678google scholar: lookup
  88. Rosa T.S., Neves R.V.P., Deus L.A., Sousa C.V., da Silva S., de Souza M.K., Moraes M.R., Rosa É.C.C.C., Andrade R.V., Korhonen M.T.. Sprint and endurance training in relation to redox balance, inflammatory status and biomarkers of aging in master athletes. Nitric Oxide 2020;102:42–51.
    doi: 10.1016/j.niox.2020.05.004pubmed: 32565116google scholar: lookup
  89. Hart P.H., Vitti G.F., Burgess D.R., Whitty G.A., Piccoli D.S., Hamilton J.A.. Potential antiinflammatory effects of interleukin 4: Suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2. Proc. Natl. Acad. Sci. USA. 1989;86:3803–3807.
    doi: 10.1073/pnas.86.10.3803pmc: PMC287229pubmed: 2786204google scholar: lookup
  90. Pedersen B.K., Toft A.D.. Effects of exercise on lymphocytes and cytokines. Br. J. Sports Med. 2000;34:246–251.
    doi: 10.1136/bjsm.34.4.246pmc: PMC1724218pubmed: 10953894google scholar: lookup
  91. Heredia J.E., Mukundan L., Chen F.M., Mueller A.A., Deo R.C., Locksley R.M., Rando T.A., Chawla A.. Type 2 Innate Signals Stimulate Fibro/Adipogenic Progenitors to Facilitate Muscle Regeneration. Cell. 2013;153:376–388.
    doi: 10.1016/j.cell.2013.02.053pmc: PMC3663598pubmed: 23582327google scholar: lookup
  92. te Velde A.A., Huijbens R.J., de Vries J.E., Figdor C.G.. IL-4 decreases Fc gamma R membrane expression and Fc gamma R-mediated cytotoxic activity of human monocytes. J. Immunol. 1990;144:3046–3051.
    doi: 10.4049/jimmunol.144.8.3046pubmed: 2139076google scholar: lookup
  93. Moyna N., Acker G., Fulton J., Weber K., Goss F., Robertson R., Tollerud D., Rabin B.. Lymphocyte Function and Cytokine Production during Incremental Exercise in Active and Sedentary Males and Females. Int. J. Sports Med. 1996;17:585–591.
    doi: 10.1055/s-2007-972899pubmed: 8973979google scholar: lookup
  94. Miglio A., Cappelli K., Capomaccio S., Mecocci S., Silvestrelli M., Antognoni M.T.. Metabolic and Biomolecular Changes Induced by Incremental Long-Term Training in Young Thoroughbred Racehorses during First Workout Season. Animals 2020;10:317.
    doi: 10.3390/ani10020317pmc: PMC7071023pubmed: 32085444google scholar: lookup
  95. Della Gatta P.A., Garnham A.P., Peake J.M., Cameron-Smith D.. Effect of exercise training on skeletal muscle cytokine expression in the elderly. Brain Behav. Immun. 2014;39:80–86.
    doi: 10.1016/j.bbi.2014.01.006pubmed: 24434040google scholar: lookup
  96. Prokopchuk O., Liu Y., Wang L., Wirth K., Schmidtbleicher D., Steinacker J.M.. Skeletal muscle IL-4, IL-4Ralpha, IL-13 and IL-13Ralpha1 expression and response to strength training. Exerc. Immunol. Rev. 2007;13:67–75.
    pubmed: 18198661
  97. Knudsen N.H., Stanya K.J., Hyde A.L., Chalom M.M., Alexander R.K., Liou Y.-H., Starost K.A., Gangl M.R., Jacobi D., Liu S.. Interleukin-13 drives metabolic conditioning of muscle to endurance exercise. Science 2020;368:eaat3987.
    doi: 10.1126/science.aat3987pmc: PMC7549736pubmed: 32355002google scholar: lookup
  98. Wilson J., De Donato M., Appelbaum B., Garcia C.T., Peters S.. Differential Expression of Innate and Adaptive Immune Genes during Acute Physical Exercise in American Quarter Horses. Animals 2023;13:308.
    doi: 10.3390/ani13020308pmc: PMC9854435pubmed: 36670847google scholar: lookup
  99. Cappelli K., Amadori M., Mecocci S., Miglio A., Antognoni M.T., Razzuoli E.. Immune Response in Young Thoroughbred Racehorses under Training. Animals 2020;10:1809.
    doi: 10.3390/ani10101809pmc: PMC7600081pubmed: 33027949google scholar: lookup
  100. Page A.E., Adam E., Arthur R., Barker V., Franklin F., Friedman R., Grande T., Hardy M., Howard B., Partridge E.. Expression of select mRNA in Thoroughbreds with catastrophic racing injuries. Equine Vet. J. 2022;54:63–73.
    doi: 10.1111/evj.13423pubmed: 33438228google scholar: lookup
  101. Guo Y., Xiao P., Lei S., Deng F., Xiao G.G., Liu Y., Chen X., Li L., Wu S., Chen Y.. How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochim. Biophys. Sin. 2008;40:426–436.
    doi: 10.1111/j.1745-7270.2008.00418.xpubmed: 18465028google scholar: lookup
  102. Davis M.S., Malayer J.R., Vandeventer L., Royer C.M., McKenzie E.C., Williamson K.K.. Cold weather exercise and airway cytokine expression. J. Appl. Physiol. 2005;98:2132–2136.
    doi: 10.1152/japplphysiol.01218.2004pubmed: 15705724google scholar: lookup
  103. Gabriel H., Schwarz L., Steffens G., Kindermann W.. Immunoregulatory Hormones, Circulating Leucocyte and Lymphocyte Subpopulations before and after Endurance Exercise of Different Intensities. Int. J. Sports Med. 1992;13:359–366.
    doi: 10.1055/s-2007-1021281pubmed: 1325959google scholar: lookup
  104. Walsh N.P., Gleeson M., Shephard R.J., Gleeson M., Woods J.A., Bishop N.C., Fleshner M., Green C., Pedersen B.K., Hoffman-Goetz L.. Position Statement Part one: Immune function and exercise. Exerc. Immunol. Rev. 2011;17:6–63.
    pubmed: 21446352
  105. Cuniberti B., Badino P., Odore R., Girardi C., Re G.. Effects induced by exercise on lymphocyte β-adrenergic receptors and plasma catecholamine levels in performance horses. Res. Vet. Sci. 2012;92:116–120.
    doi: 10.1016/j.rvsc.2010.11.002pubmed: 21168179google scholar: lookup
  106. Malinowski K., Kearns C.F., Guirnalda P.D., Roegner V., McKeever K.H.. Effect of chronic clenbuterol administration and exercise training on immune function in horses. J. Anim. Sci. 2004;82:3500–3507.
    doi: 10.2527/2004.82123500xpubmed: 15537770google scholar: lookup
  107. Nieman D.C.. Exercise, Infection, and Immunity. Int. J. Sports Med. 1994;15:S131–S141.
    doi: 10.1055/s-2007-1021128pubmed: 7883395google scholar: lookup
  108. Nesse L.L., Johansen G.I., Blom A.K.. Effects of racing on lymphocyte proliferation in horses. Am. J. Vet. Res. 2002;63:528–530.
    doi: 10.2460/ajvr.2002.63.528pubmed: 11939314google scholar: lookup
  109. Peake J.M., Neubauer O., Walsh N.P., Simpson R.J.. Recovery of the immune system after exercise. J. Appl. Physiol. 2017;122:1077–1087.
    doi: 10.1152/japplphysiol.00622.2016pubmed: 27909225google scholar: lookup
  110. Siedlik J.A., Benedict S.H., Landes E.J., Weir J.P., Vardiman J.P., Gallagher P.M.. Acute bouts of exercise induce a suppressive effect on lymphocyte proliferation in human subjects: A meta-analysis. Brain Behav. Immun. 2016;56:343–351.
    doi: 10.1016/j.bbi.2016.04.008pubmed: 27103377google scholar: lookup
  111. Pedersen B.K., Ullum H.. NK cell response to physical activity: Possible mechanisms of action. Med. Sci. Sports Exerc. 1994;26:140–146.
    doi: 10.1249/00005768-199402000-00003pubmed: 8164530google scholar: lookup
  112. Kurcz E.V., Lawrence L.M., Kelley K.W., Miller P.A.. The effect of intense exercise on the cell-mediated immune response of horses. J. Equine Vet. Sci. 1988;8:237–239.
    doi: 10.1016/s0737-0806(88)80015-7google scholar: lookup
  113. Nielsen H.B., Pedersen B.K.. Lymphocyte proliferation in response to exercise. Eur. J. Appl. Physiol. 1997;75:375–379.
    doi: 10.1007/s004210050175pubmed: 9189722google scholar: lookup
  114. Shinkai S., Kohno H., Kimura K., Komura T., Asai H., Inai R., Oka K., Kurokawa Y., Shephard R.J.. Physical activity and immune senescence in men. Med. Sci. Sports Exerc. 1995;27:1516–1526.
    doi: 10.1249/00005768-199511000-00008pubmed: 8587488google scholar: lookup
  115. Simpson R.J., Spielmann G., Hanley P., Bollard C.M.. A single bout of exercise augments the expansion of multi-virus specific T-cells in healthy humans. Brain Behav. Immun. 2014;40:e51.
    doi: 10.1016/j.bbi.2014.06.197google scholar: lookup
  116. Hines M.T., Schott H.C. II, Bayly W.M., Leroux A.J.. Exercise and Immunity: A Review with Emphasis on the Horse. J. Vet. Intern. Med. 1996;10:280–289.
    doi: 10.1111/j.1939-1676.1996.tb02063.xpubmed: 8884712google scholar: lookup
  117. Kajiura J.S., MacDougall J.D., Ernst P.B., Younglai E.V.. Immune response to changes in training intensity and volume in runners. Med. Sci. Sports Exerc. 1995;27:1111–1117.
    doi: 10.1249/00005768-199508000-00002pubmed: 7476053google scholar: lookup
  118. McCarthy D.A., Dale M.M.. The Leucocytosis of Exercise: A Review and Model. Sports Med. 1988;6:333–363.
    doi: 10.2165/00007256-198806060-00002pubmed: 3068772google scholar: lookup
  119. Tvede N., Kappel M., Halkjœr-Kristensen J., Galbo H., Pedersen B.K.. The Effect of Light, Moderate and Severe Bicycle Exercise on Lymphocyte Subsets, Natural and Lymphokine Activated Killer Cells, Lymphocyte Proliferative Response and Interleukin 2 Production. Int. J. Sports Med. 1993;14:275–282.
    doi: 10.1055/s-2007-1021177pubmed: 8365836google scholar: lookup
  120. Witkowska-Piłaszewicz O., Pingwara R., Szczepaniak J., Winnicka A.. The Effect of the Clenbuterol—β2-Adrenergic Receptor Agonist on the Peripheral Blood Mononuclear Cells Proliferation, Phenotype, Functions, and Reactive Oxygen Species Production in Race Horses In Vitro. Cells 2021;10:936.
    doi: 10.3390/cells10040936pmc: PMC8072563pubmed: 33920705google scholar: lookup
  121. Hamza E., Gerber V., Steinbach F., Marti E.. Equine CD4+ CD25high T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro. Immunology 2011;134:292–304.
    doi: 10.1111/j.1365-2567.2011.03489.xpmc: PMC3209569pubmed: 21977999google scholar: lookup
  122. Perry C., Pick M., Bdolach N., Hazan-Halevi I., Kay S., Berr I., Reches A., Harishanu Y., Grisaru D.. Endurance Exercise Diverts the Balance between Th17 Cells and Regulatory T Cells. PLoS ONE 2013;8:e74722.
    doi: 10.1371/journal.pone.0074722pmc: PMC3793976pubmed: 24130669google scholar: lookup
  123. Rehm K., Sunesara I., Marshall G.D.. Increased Circulating Anti-inflammatory Cells in Marathon-trained Runners. Int. J. Sports Med. 2015;36:832–836.
    doi: 10.1055/s-0035-1547218pubmed: 26038877google scholar: lookup
  124. Robbin M.G., Wagner B., Noronha L.E., Antczak D.F., de Mestre A.M.. Subpopulations of equine blood lymphocytes expressing regulatory T cell markers. Vet. Immunol. Immunopathol. 2011;140:90–101.
    doi: 10.1016/j.vetimm.2010.11.020pubmed: 21208665google scholar: lookup
  125. Timmons B.W., Cieslak T.. Human natural killer cell subsets and acute exercise: A brief review. Exerc. Immunol. Rev. 2008;14:8–23.
    pubmed: 19203081
  126. Zimmer P., Schenk A., Kieven M., Holthaus M., Lehmann J., Lövenich L., Bloch W.. Exercise induced alterations in NK-cell cytotoxicity—Methodological issues and future perspectives. Exerc. Immunol. Rev. 2017;23:66–81.
    pubmed: 28230531
  127. Hsia J.-Y., Chen J.-T., Chen C.-Y., Hsu C.-P., Miaw J., Huang Y.-S., Yang C.-Y.. Prognostic significance of intratumoral natural killer cells in primary resected esophageal squamous cell carcinoma. Chang Gung Med. J. 2005;28:335–340.
    pubmed: 16086548
  128. Llavero F., Alejo L.B., Fiuza-Luces C., López Soto A., Valenzuela P.L., Castillo-García A., Morales J.S., Fernández D., Aldazabal I.P., Ramírez M.. Exercise training effects on natural killer cells: A preliminary proteomics and systems biology approach. Exerc. Immunol. Rev. 2021;27:125–141.
    pubmed: 33965896
  129. Rincón H.G., Solomon G.F., Benton D., Rubenstein L.Z.. Exercise in frail elderly men decreases natural killer cell activity. Aging Clin. Exp. Res. 1996;8:109–112.
    doi: 10.1007/bf03339564pubmed: 8737609google scholar: lookup
  130. Zouhal H., Jacob C., Delamarche P., Gratas-Delamarche A.. Catecholamines and the Effects of Exercise, Training and Gender. Sports Med. 2008;38:401–423.
    doi: 10.2165/00007256-200838050-00004pubmed: 18416594google scholar: lookup
  131. Moro-García M.A., Fernández-García B., Echeverría A., Rodríguez-Alonso M., Suárez-García F.M., Solano-Jaurrieta J.J., López-Larrea C., Alonso-Arias R.. Frequent participation in high volume exercise throughout life is associated with a more differentiated adaptive immune response. Brain Behav. Immun. 2014;39:61–74.
    doi: 10.1016/j.bbi.2013.12.014pubmed: 24384467google scholar: lookup
  132. Viveiros M.M., Antczak D.F.. Characterization of equine natural killer and IL-2 stimulated lymphokine activated killer cell populations. Dev. Comp. Immunol. 1999;23:521–532.
    doi: 10.1016/s0145-305x(99)00030-0pubmed: 10512462google scholar: lookup
  133. Lunn D.P., Schram B.R., Vagnoni K.E., Schobert C.S., Horohov D.W., Ginther O.J.. Positive selection of EqCD8+ precursors increases equine lymphokine-activated killing. Vet. Immunol. Immunopathol. 1996;53:1–13.
    doi: 10.1016/0165-2427(96)05554-7pubmed: 8941964google scholar: lookup
  134. Horohov D.. Equine Exercise Physiology. 2008. Immunological responses to exercise and training; pp. 410–422.
  135. Ziegler-Heitbrock L., Ancuta P., Crowe S., Dalod M., Grau V., Hart D.N., Leenen P.J.M., Liu Y.-J., MacPherson G., Randolph G.J.. Nomenclature of monocytes and dendritic cells in blood. Blood 2010;116:e74–e80.
    doi: 10.1182/blood-2010-02-258558pubmed: 20628149google scholar: lookup
  136. Narasimhan P.B., Marcovecchio P., Hamers A.A.J., Hedrick C.C.. Nonclassical Monocytes in Health and Disease. Annu. Rev. Immunol. 2019;37:439–456.
    doi: 10.1146/annurev-immunol-042617-053119pubmed: 31026415google scholar: lookup
  137. Kiku Y., Kusano K.-I., Miyake H., Fukuda S., Takahashi J., Inotsume M., Hirano S., Yoshihara T., Toribio R.E., Okada H.. Flow Cytometric Analysis of Peripheral Blood Mononuclear Cells Induced by Experimental Endotoxemia in Horse. J. Vet. Med. Sci. 2003;65:857–863.
    doi: 10.1292/jvms.65.857pubmed: 12951417google scholar: lookup
  138. Sarkar S., Chelvarajan L., Go Y.Y., Cook F., Artiushin S., Mondal S., Anderson K., Eberth J., Timoney P.J., Kalbfleisch T.S.. Equine Arteritis Virus Uses Equine CXCL16 as an Entry Receptor. J. Virol. 2016;90:3366–3384.
    doi: 10.1128/jvi.02455-15pmc: PMC4794689pubmed: 26764004google scholar: lookup
  139. Gibbons N., Goulart M.R., Chang Y.-M., Efstathiou K., Purcell R., Wu Y., Peters L.M., Turmaine M., Szladovits B., Garden O.A.. Phenotypic heterogeneity of peripheral monocytes in healthy dogs. Vet. Immunol. Immunopathol. 2017;190:26–30.
    doi: 10.1016/j.vetimm.2017.06.007pubmed: 28778319google scholar: lookup
  140. Blanks A.M., Wagamon T.T., Lafratta L., Sisk M.G., Senter M.B., Pedersen L.N., Bohmke N., Shah A., Mihalick V.L., Franco R.L.. Impact of physical activity on monocyte subset CCR2 expression and macrophage polarization following moderate intensity exercise. Brain Behav. Immun.—Health 2020;2:100033.
    doi: 10.1016/j.bbih.2019.100033pmc: PMC8474621pubmed: 38377416google scholar: lookup
  141. Steppich B., Dayyani F., Gruber R., Lorenz R., Mack M., Ziegler-Heitbrock H.W.L.. Selective mobilization of CD14+CD16+ monocytes by exercise. Am. J. Physiol. Physiol. 2000;279:C578–C586.
    doi: 10.1152/ajpcell.2000.279.3.c578pubmed: 10942707google scholar: lookup
  142. Timmerman K.L., Flynn M.G., Coen P.M., Markofski M.M., Pence B.D.. Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: A role in the anti-inflammatory influence of exercise?. J. Leukoc. Biol. 2008;84:1271–1278.
    doi: 10.1189/jlb.0408244pubmed: 18664531google scholar: lookup
  143. Cupps T.R., Fauci A.S.. Corticosteroid-Mediated Immunoregulation in Man. Immunol. Rev. 1982;65:133–155.
    doi: 10.1111/j.1600-065x.1982.tb00431.xpubmed: 6214495google scholar: lookup
  144. Miglio A., Falcinelli E., Mezzasoma A.M., Cappelli K., Mecocci S., Gresele P., Antognoni M.T.. Effect of First Long-Term Training on Whole Blood Count and Blood Clotting Parameters in Thoroughbreds. Animals 2021;11:447.
    doi: 10.3390/ani11020447pmc: PMC7915801pubmed: 33572086google scholar: lookup
  145. Moghadam-Kia S., Oddis C.V., Aggarwal R.. Approach to asymptomatic creatine kinase elevation. Clevel. Clin. J. Med. 2016;83:37–42.
    doi: 10.3949/ccjm.83a.14120pmc: PMC4871266pubmed: 26760521google scholar: lookup
  146. Marqués-Jiménez D., Calleja-González J., Arratibel I., Delextrat A., Terrados N.. Are compression garments effective for the recovery of exercise-induced muscle damage? A systematic review with meta-analysis. Physiol. Behav. 2016;153:133–148.
    doi: 10.1016/j.physbeh.2015.10.027pubmed: 26522739google scholar: lookup
  147. Bekkelund S.I., Johnsen S.H.. Creatine kinase is associated with reduced inflammation in a general population: The Tromsø study. PLoS ONE 2018;13:e0198133.
    doi: 10.1371/journal.pone.0198133pmc: PMC5973606pubmed: 29813131google scholar: lookup
  148. Baird M.F., Graham S.M., Baker J.S., Bickerstaff G.F.. Creatine-Kinase- and Exercise-Related Muscle Damage Implications for Muscle Performance and Recovery. J. Nutr. Metab. 2012;2012:960363.
    doi: 10.1155/2012/960363pmc: PMC3263635pubmed: 22288008google scholar: lookup
  149. Paillot R., Hannant D., Kydd J., Daly J.. Vaccination against equine influenza: Quid novi?. Vaccine 2006;24:4047–4061.
    doi: 10.1016/j.vaccine.2006.02.030pubmed: 16545507google scholar: lookup
  150. Craigo J.K., Leroux C., Howe L., Steckbeck J.D., Cook S.J., Issel C.J., Montelaro R.C.. Transient immune suppression of inapparent carriers infected with a principal neutralizing domain-deficient equine infectious anaemia virus induces neutralizing antibodies and lowers steady-state virus replication. J. Gen. Virol. 2002;83:1353–1359.
    doi: 10.1099/0022-1317-83-6-1353pubmed: 12029150google scholar: lookup
  151. Leroux C., Montelaro R.C., Cadoré J.-L.. Equine Infectious Anemia Virus (EIAV): What has HIV’s country cousin got to tell us?. Vet. Res. 2004;35:485–512.
    doi: 10.1051/vetres:2004020pubmed: 15236678google scholar: lookup
  152. Capomaccio S., Cappelli K., Spinsanti G., Mencarelli M., Muscettola M., Felicetti M., Supplizi A.V., Bonifazi M.. Athletic humans and horses: Comparative analysis of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) expression in peripheral blood mononuclear cells in trained and untrained subjects at rest. BMC Physiol. 2011;11:3.
    doi: 10.1186/1472-6793-11-3pmc: PMC3036646pubmed: 21255427google scholar: lookup
  153. Harris M.D.. Infectious Disease in Athletes. Curr. Sports Med. Rep. 2011;10:84–89.
    doi: 10.1249/JSR.0b013e3182142381pubmed: 21623289google scholar: lookup
  154. Karagianni A.E., Lisowski Z.M., Hume D.A., Scott Pirie R.. The equine mononuclear phagocyte system: The relevance of the horse as a model for understanding human innate immunity. Equine Vet. J. 2021;53:231–249.
    doi: 10.1111/evj.13341pubmed: 32881079google scholar: lookup
  155. Wilke M.M., Nydam D.V., Nixon A.J.. Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model. J. Orthop. Res. 2007;25:913–925.
    doi: 10.1002/jor.20382pubmed: 17405160google scholar: lookup
  156. Godwin E.E., Young N.J., Dudhia J., Beamish I.C., Smith R.K.W.. Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet. J. 2012;44:25–32.
    doi: 10.1111/j.2042-3306.2011.00363.xpubmed: 21615465google scholar: lookup
  157. Halaris A.E., Belendiuk K.T., Freedman D.X.. Antidepressant drugs affect dopamine uptake. Biochem. Pharmacol. 1975;24:1896–1898.
    doi: 10.1016/0006-2952(75)90412-8pubmed: 19google scholar: lookup
  158. Malda J., Benders K.E.M., Klein T.J., de Grauw J.C., Kik M.J.L., Hutmacher D.M., Saris D.B.F., van Weeren P.R., Dhert W.J.A.. Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyles. Osteoarthr. Cartil. 2012;20:1147–1151.
    doi: 10.1016/j.joca.2012.06.005pubmed: 22781206google scholar: lookup
  159. Goodrich L.R., Nixon A.J.. Medical treatment of osteoarthritis in the horse—A review. Vet. J. 2006;171:51–69.
    doi: 10.1016/j.tvjl.2004.07.008pubmed: 16427582google scholar: lookup
  160. Nelson B.B., Goodrich L.R., Barrett M.F., Grinstaff M.W., Kawcak C.E.. Use of contrast media in computed tomography and magnetic resonance imaging in horses: Techniques, adverse events and opportunities. Equine Vet. J. 2017;49:410–424.
    doi: 10.1111/evj.12689pubmed: 28407291google scholar: lookup
  161. Nelson B.B., Kawcak C.E., Barrett M.F., McIlwraith C.W., Grinstaff M.W., Goodrich L.R.. Recent advances in articular cartilage evaluation using computed tomography and magnetic resonance imaging. Equine Vet. J. 2018;50:564–579.
    doi: 10.1111/evj.12808pubmed: 29344988google scholar: lookup
  162. Dudhia J., Scott C.M., Draper E.R.C., Heinegård D., Pitsillides A.A., Smith R.K.. Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity. Aging Cell. 2007;6:547–556.
    doi: 10.1111/j.1474-9726.2007.00307.xpubmed: 17578513google scholar: lookup
  163. Mokone G.G., Gajjar M., September A.V., Schwellnus M.P., Greenberg J., Noakes T.D., Collins M.. The Guanine-Thymine Dinucleotide Repeat Polymorphism within the Tenascin-C Gene is Associated with Achilles Tendon Injuries. Am. J. Sports Med. 2005;33:1016–1021.
    doi: 10.1177/0363546504271986pubmed: 15983124google scholar: lookup
  164. Mokone G.G., Schwellnus M.P., Noakes T.D., Collins M.. The COL5A1 gene and Achilles tendon pathology. Scand. J. Med. Sci. Sports. 2006;16:19–26.
    doi: 10.1111/j.1600-0838.2005.00439.xpubmed: 16430677google scholar: lookup
  165. Tully L.J., Murphy A.M., Smith R.K.W., Hulin-Curtis S.L., Verheyen K.L.P., Price J.S.. Polymorphisms in TNC and COL5A1 genes are associated with risk of superficial digital flexor tendinopathy in National Hunt Thoroughbred racehorses. Equine Vet. J. 2014;46:289–293.
    doi: 10.1111/evj.12134pubmed: 23906005google scholar: lookup
  166. Coleman S.J., Zeng Z., Hestand M.S., Liu J., Macleod J.N.. Analysis of Unannotated Equine Transcripts Identified by mRNA Sequencing. PLoS ONE 2013;8:e70125.
    doi: 10.1371/journal.pone.0070125pmc: PMC3726457pubmed: 23922931google scholar: lookup
  167. Raudsepp T., Finno C.J., Bellone R.R., Petersen J.L.. Ten years of the horse reference genome: Insights into equine biology, domestication and population dynamics in the post-genome era. Anim. Genet. 2019;50:569–597.
    doi: 10.1111/age.12857pmc: PMC6825885pubmed: 31568563google scholar: lookup
  168. Simpson R.J., Kunz H., Agha N., Graff R.. Progress in Molecular Biology and Translational Science. 2015. Exercise and the Regulation of Immune Functions; pp. 355–380.
    pubmed: 26477922
  169. Suzuki K., Totsuka M., Nakaji S., Yamada M., Kudoh S., Liu Q., Sugawara K., Yamaya K., Sato K.. Endurance exercise causes interaction among stress hormones, cytokines, neutrophil dynamics, and muscle damage. J. Appl. Physiol. 1999;87:1360–1367.
    doi: 10.1152/jappl.1999.87.4.1360pubmed: 10517764google scholar: lookup
  170. Andriichuk A., Tkachenko H.. Effect of gender and exercise on haematological and biochemical parameters in Holsteiner horses. J. Anim. Physiol. Anim. Nutr. 2017;101:e404–e413.
    doi: 10.1111/jpn.12620pubmed: 28066938google scholar: lookup
  171. Gatti R., De Palo E.F.. An update: Salivary hormones and physical exercise. Scand. J. Med. Sci. Sports. 2011;21:157–169.
    doi: 10.1111/j.1600-0838.2010.01252.xpubmed: 21129038google scholar: lookup
  172. Hill E.E., Zack E., Battaglini C., Viru M., Viru A., Hackney A.C.. Exercise and circulating Cortisol levels: The intensity threshold effect. J. Endocrinol. Investig. 2008;31:587–591.
    doi: 10.1007/bf03345606pubmed: 18787373google scholar: lookup
  173. Kirschbaum C., Hellhammer D.H.. Salivary cortisol in psychoneuroendocrine research: Recent developments and applications. Psychoneuroendocrinology 1994;19:313–333.
    doi: 10.1016/0306-4530(94)90013-2pubmed: 8047637google scholar: lookup
  174. Witkowska-Piłaszewicz O., Grzędzicka J., Seń J., Czopowicz M., Żmigrodzka M., Winnicka A., Cywińska A., Carter C.. Stress response after race and endurance training sessions and competitions in Arabian horses. Prev. Vet. Med. 2021;188:105265.
    doi: 10.1016/j.prevetmed.2021.105265pubmed: 33497894google scholar: lookup
  175. Zamani A., Salehi I., Alahgholi-Hajibehzad M.. Moderate Exercise Enhances the Production of Interferon-γ and Interleukin-12 in Peripheral Blood Mononuclear Cells. Immune Netw. 2017;17:186–191.
    doi: 10.4110/in.2017.17.3.186pmc: PMC5484649pubmed: 28680380google scholar: lookup
  176. Suzuki K., Nakaji S., Kurakake S., Totsuka M., Sato K., Kuriyama T., Fujimoto H., Shibusawa K., Machida K., Sugawara K.. Exhaustive exercise and type-1/type-2 cytokine balance with special focus on interleukin-12 p40/p70. Exerc. Immunol. Rev. 2003;9:48–57.
    pubmed: 14686094
  177. Luk H.-Y., Levitt D.E., Lee E.C., Ganio M.S., McDermott B.P., Kupchak B.R., McFarlin B.K., Hill D.W., Armstrong L.E., Vingren J.L.. Pro- and anti-inflammatory cytokine responses to a 164-km road cycle ride in a hot environment. Eur. J. Appl. Physiol. 2016;116:2007–2015.
    doi: 10.1007/s00421-016-3452-5pubmed: 27522585google scholar: lookup
  178. MacDonald C., Wojtaszewski J.F.P., Pedersen B.K., Kiens B., Richter E.A.. Interleukin-6 release from human skeletal muscle during exercise: Relation to AMPK activity. J. Appl. Physiol. 2003;95:2273–2277.
    doi: 10.1152/japplphysiol.00242.2003pubmed: 12937023google scholar: lookup
  179. Mach N., Ramayo-Caldas Y., Clark A., Moroldo M., Robert C., Barrey E., López J.M., Le Moyec L.. Understanding the response to endurance exercise using a systems biology approach: Combining blood metabolomics, transcriptomics and miRNomics in horses. BMC Genom. 2017;18:187.
    doi: 10.1186/s12864-017-3571-3pmc: PMC5316211pubmed: 28212624google scholar: lookup
  180. Bernecker C., Scherr J., Schinner S., Braun S., Scherbaum W.A., Halle M.. Evidence for an exercise induced increase of TNF-α and IL-6 in marathon runners. Scand. J. Med. Sci. Sports. 2013;23:207–214.
    doi: 10.1111/j.1600-0838.2011.01372.xpubmed: 22092703google scholar: lookup
  181. Lefkowitz R.J.. Identification of adenylate cyclase-coupled beta-adrenergic receptors with radiolabeled beta-adrenergic antagonists. Biochem. Pharmacol. 1975;24:1651–1658.
    doi: 10.1016/0006-2952(75)90001-5pubmed: 11google scholar: lookup
  182. Eriksson B., Hedfors E.. The Effect of Adrenaline, Insulin and Hydrocortisone on Human Peripheral Blood Lymphocytes Studied by Cell Surface Markers. Scand. J. Haematol. 1977;18:121–128.
    doi: 10.1111/j.1600-0609.1977.tb02081.xpubmed: 300173google scholar: lookup
  183. Crary B., Hauser S.L., Borysenko M., Kutz I., Hoban C., Ault K.A., Weiner H.L., Benson H.. Epinephrine-induced changes in the distribution of lymphocyte subsets in peripheral blood of humans. J. Immunol. 1983;131:1178–1181.
    doi: 10.4049/jimmunol.131.3.1178pubmed: 6224849google scholar: lookup
  184. Rumpf C., Proschinger S., Schenk A., Bloch W., Lampit A., Javelle F., Zimmer P.. The Effect of Acute Physical Exercise on NK-Cell Cytolytic Activity: A Systematic Review and Meta-Analysis. Sports Med. 2021;51:519–530.
    doi: 10.1007/s40279-020-01402-9pmc: PMC7900082pubmed: 33398798google scholar: lookup
  185. Gavrieli R., Ashlagi-Amiri T., Eliakim A., Nemet D., Zigel L., Berger-Achituv S., Falk B., Wolach B.. The effect of aerobic exercise on neutrophil functions. Med. Sci. Sports Exerc. 2008;40:1623–1628.
    doi: 10.1249/mss.0b013e318176b963pubmed: 18685529google scholar: lookup
  186. Wong C.W., Smith S.E., Thong Y.H., Opdebeeck J.P., Thornton J.R.. Effects of exercise stress on various immune functions in horses. Am. J. Vet. Res. 1992;53:1414–1417.
    doi: 10.2460/ajvr.1992.53.08.1414pubmed: 1510320google scholar: lookup

Citations

This article has been cited 6 times.
  1. Milczek-Haduch D, Żmigrodzka M, Kiełbik P, Świderska B, Olędzki J, Witkowska-Piłaszewicz O. Comparative Analysis of Extracellular Vesicle Isolation From Equine Serum and Plasma Using Two Isolation Methods With Structural and Proteomic Validation. FASEB J 2026 Jan 31;40(2):e71472.
    doi: 10.1096/fj.202504053Rpubmed: 41549528google scholar: lookup
  2. Takahashi K, Mukai K, Takahashi Y, Ebisuda Y, Sugiyama F, Hatta H, Kitaoka Y. Effects of hypoxia and hyperoxia on exercise-induced metabolomic and transcriptomic profiles in equine skeletal muscle. J Exp Biol 2025 Dec 15;228(24).
    doi: 10.1242/jeb.250956pubmed: 41199666google scholar: lookup
  3. Witkowska-Piłaszewicz O, Nowicka-Kazmierczak M, Pietrzak P, Marycz K. Mitohormesis and Regeneration: Natural Compounds Chlorogenic Acid (CGA) and Isovanillic Acid 3-O-sulfate (IVAS) Boost Muscle Cell Recovery in the Equine Athlete Model. Stem Cell Rev Rep 2025 Nov;21(8):2654-2666.
    doi: 10.1007/s12015-025-10959-9pubmed: 40900286google scholar: lookup
  4. Tolnai C, O'Sullivan C, Lőrincz M, Karvouni M, Tenk M, Marosi A, Forgách P, Paszerbovics B, Wagenhoffer Z, Kutasi O. Cellular Immune Response in Horses After West Nile Neuroinvasive Disease. Animals (Basel) 2025 Aug 11;15(16).
    doi: 10.3390/ani15162352pubmed: 40867680google scholar: lookup
  5. Kiełbik P, Witkowska-Piłaszewicz O. Iron Status in Sport Horses: Is It Important for Equine Athletes?. Int J Mol Sci 2025 Jun 12;26(12).
    doi: 10.3390/ijms26125653pubmed: 40565115google scholar: lookup
  6. Aragona F, Giannetto C, Piccione G, Arfuso F, Arrigo F, Costa A, De Caro S, Cannuli A, Fazio F. Effect of time of day and physical exercise on inflammatory biomarkers in athletic horses. Front Vet Sci 2025;12:1608770.
    doi: 10.3389/fvets.2025.1608770pubmed: 40534779google scholar: lookup
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.